scholarly journals Functionalized Large-Pore Mesoporous Silica Microparticles for Gefitinib and Doxorubicin Codelivery

Materials ◽  
2019 ◽  
Vol 12 (5) ◽  
pp. 766 ◽  
Author(s):  
Yan Li ◽  
Fangxiang Song ◽  
Liang Cheng ◽  
Jin Qian ◽  
Qianlin Chen
Keyword(s):  
Electron Microscopy ◽  
Mesoporous Silica ◽  
Photoelectron Spectroscopy ◽  
Human Cancer ◽  
Synergistic Effects ◽  
Human Cancer Cells ◽  
Large Pore ◽  
Silica Microparticles ◽  
Dual Drug

Large-pore coralline mesoporous silica microparticles (CMS) were synthesized using the triblock polymer PEG-b-PEO-b-PEG and a hydrothermal method. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) revealed the coralline morphology of the fabricated materials. The Brunauer–Emmett–Teller (BET) method and the Barrett–Joyner–Halenda (BJH) model confirmed the existence of large pores (20 nm) and of a tremendous specific surface area (663.865 m2·g−1) and pore volume (0.365 cm3·g−1). A novel pH-sensitive multiamine-chain carboxyl-functionalized coralline mesoporous silica material (CMS–(NH)3–COOH) was obtained via a facile “grafting-to” approach. X-ray photoelectron spectroscopy (XPS) and Fourier-transform infrared spectroscopy (FT-IR) validated the effective interfacial functionalization of CMS with carboxyl and multiamine chains. The encapsulation and release behavior of the dual drug (gefitinib (GB) and doxorubicin (DOX)) was also investigated. It was found that CMS–(NH)3–COOH allows rapid encapsulation with a high loading capacity of 47.36% for GB and 26.74% for DOX. Furthermore, the release profiles reveal that CMS–(NH)3–COOH can preferably control the release of DOX and GB. The accumulative release rates of DOX and GB were 32.03% and 13.66%, respectively, at a low pH (pH 5.0), while they reduced to 8.45% and 4.83% at pH 7.4. Moreover, all of the modified silica nanoparticles exhibited a high biocompatibility with a low cytotoxicity. In particular, the cytotoxicity of both of these two drugs was remarkably reduced after being encapsulated. CMS–(NH)3–COOH@GB@DOX showed tremendously synergistic effects of the dual drug in the antiproliferation and apoptosis of A549 human cancer cells in vitro.

Structure-Reactivity Relationships on Substrates and Inhibitors of the Lysine Deacylase Sirtuin 2 from Schistosoma Mansoni (SmSirt2)

2019 ◽  
Author(s):  
Daria Monaldi ◽  
Dante Rotili ◽  
Julien Lancelot ◽  
Martin Marek ◽  
Nathalie Wössner ◽  
...  
Keyword(s):  
Schistosoma Mansoni ◽  
Human Cancer ◽  
Egg Laying ◽  
Human Cancer Cells ◽  
Parasite Survival ◽  
Survival And Reproduction ◽  
Emergence Of Resistance ◽  
First Time ◽  
Parasitic Life Cycle

The only drug for treatment of Schistosomiasis is Praziquantel, and the possible emergence of resistance makes research on novel therapeutic agents necessary. Targeting of Schistosoma mansoni epigenetic enzymes, which regulate the parasitic life cycle, emerged as promising approach. Due to the strong effects of human Sirtuin inhibitors on parasite survival and reproduction, Schistosoma sirtuins were postulated as therapeutic targets. In vitro testing of synthetic substrates of S. mansoni Sirtuin 2 (SmSirt2) and kinetic experiments on a myristoylated peptide demonstrated lysine long chain deacylation as an intrinsic SmSirt2 activity for the first time. Focused in vitro screening of the GSK Kinetobox library and structure-activity relationships (SAR) of identified hits, led to the first SmSirt2 inhibitors with activity in the low micromolar range. Several SmSirt2 inhibitors showed potency against both larval schistosomes (viability) and adult worms (pairing, egg laying) in culture without general toxicity to human cancer cells.<br>

scholarly journals A New Smoothened Antagonist Bearing the Purine Scaffold Shows Antitumour Activity In Vitro and In Vivo

2021 ◽  
Vol 22 (16) ◽  
pp. 8372
Author(s):  
Ana María Zárate ◽  
Christian Espinosa-Bustos ◽  
Simón Guerrero ◽  
Angélica Fierro ◽  
Felipe Oyarzún-Ampuero ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Human Cancer ◽  
Antitumour Activity ◽  
Anticancer Compounds ◽  
Human Cancer Cells ◽  
Cycle Arrest ◽  
Apoptosis Inducer ◽  
Purine Ring

The Smoothened (SMO) receptor is the most druggable target in the Hedgehog (HH) pathway for anticancer compounds. However, SMO antagonists such as vismodegib rapidly develop drug resistance. In this study, new SMO antagonists having the versatile purine ring as a scaffold were designed, synthesised, and biologically tested to provide an insight to their mechanism of action. Compound 4s was the most active and the best inhibitor of cell growth and selectively cytotoxic to cancer cells. 4s induced cell cycle arrest, apoptosis, a reduction in colony formation and downregulation of PTCH and GLI1 expression. BODIPY-cyclopamine displacement assays confirmed 4s is a SMO antagonist. In vivo, 4s strongly inhibited tumour relapse and metastasis of melanoma cells in mice. In vitro, 4s was more efficient than vismodegib to induce apoptosis in human cancer cells and that might be attributed to its dual ability to function as a SMO antagonist and apoptosis inducer.

Rhodium(i) N-heterocyclic carbene complexes: synthesis and cytotoxic properties

2021 ◽  
Vol 45 (11) ◽  
pp. 5176-5183
Author(s):  
Ichraf Slimani ◽  
Serap Şahin-Bölükbaşı ◽  
Mustafa Ulu ◽  
Enes Evren ◽  
Nevin Gürbüz ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Mtt Assay ◽  
Incubation Time ◽  
Human Cancer ◽  
Cytotoxic Activities ◽  
Carbene Complexes ◽  
Human Cancer Cells ◽  
Benzimidazolium Salts ◽  
Ht 29

A series of benzimidazolium salts and their [RhCl(NHC)(COD)] complexes were synthesized. All compounds were screened for in vitro cytotoxic activities against a panel of human cancer cells (HT-29 colon, Ishikawa endometrial, U-87 glioblastoma) using the MTT assay for 48 h incubation time.

PLATELET ACTIVATION BY HUMAN CANCER CELLS GROWN “IN VITRO” OR DISSOCIATED FROM TUMOUR TISSUES

1987 ◽  
Author(s):  
G Grignani ◽  
L Pacchiarini ◽  
M Zucchella ◽  
L Dezza ◽  
S C Rizzo
Keyword(s):  
Platelet Aggregation ◽  
Platelet Activation ◽  
Human Cancer ◽  
Iodoacetic Acid ◽  
Tumour Cells ◽  
Human Cancer Cells ◽  
Human Tumour Cells ◽  
Dissociated Cells ◽  
Lymphoblastic Cells

The mechanisms of platelet activation by human tumour cells grown “in vitro” or freshly dissociated from tumour tissues have been investigated.MoCCL human T-lymphoblastic cells cultured “in vitro” induced platelet aggregation through the production of ADP, as evidenced by inhibition of the effect by apyrase. The maximum of ADP production by tumour cells was reached after 1 hour and was 225 p moles/106 cells.On the contrary, platelet aggregation induced by 5637 human bladder carcinoma cells was not inhibited by apyrase, but was abolished by hirudin, indicating the important role of thrombin in this effect.Tumour cells dissociated from 3 breast carcinomas showed a very high platelet aggregating activity, which was not inhibited by hirudin or apyrase, but was abolished by iodoacetic acid, suggesting a role for a cystein-protease in platelet activation.These results confirm that platelets can be activated by tumour cells through different mechanisms; they also suggest that the methods employed to obtain the tumour cells can influence the results, probably because of the different cell populations which are present in the dissociated tumour tissues.Informations obtained with freshly dissociated cells are interesting, because this method has been used seldom so far and because it provides a more physiological approach to the study of the interactions of tumours and platelets.

scholarly journals Design and In Vitro Study of a Dual Drug-Loaded Delivery System Produced by Electrospinning for the Treatment of Acute Injuries of the Central Nervous System

Pharmaceutics ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 848
Author(s):  
Luisa Stella Dolci ◽  
Rosaria Carmela Perone ◽  
Roberto Di Gesù ◽  
Mallesh Kurakula ◽  
Chiara Gualandi ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Delivery System ◽  
Synergistic Effects ◽  
In Vitro Release ◽  
Health Priorities ◽  
The Central Nervous System ◽  
Vitro Release ◽  
Dual Drug

Vascular and traumatic injuries of the central nervous system are recognized as global health priorities. A polypharmacology approach that is able to simultaneously target several injury factors by the combination of agents having synergistic effects appears to be promising. Herein, we designed a polymeric delivery system loaded with two drugs, ibuprofen (Ibu) and thyroid hormone triiodothyronine (T3) to in vitro release the suitable amount of the anti-inflammation and the remyelination drug. As a production method, electrospinning technology was used. First, Ibu-loaded micro (diameter circa 0.95–1.20 µm) and nano (diameter circa 0.70 µm) fibers were produced using poly(l-lactide) PLLA and PLGA with different lactide/glycolide ratios (50:50, 75:25, and 85:15) to select the most suitable polymer and fiber diameter. Based on the in vitro release results and in-house knowledge, PLLA nanofibers (mean diameter = 580 ± 120 nm) loaded with both Ibu and T3 were then successfully produced by a co-axial electrospinning technique. The in vitro release studies demonstrated that the final Ibu/T3 PLLA system extended the release of both drugs for 14 days, providing the target sustained release. Finally, studies in cell cultures (RAW macrophages and neural stem cell-derived oligodendrocyte precursor cells—OPCs) demonstrated the anti-inflammatory and promyelinating efficacy of the dual drug-loaded delivery platform.

scholarly journals Study of the antiproliferative potential of seed extracts from Northeastern Brazilian plants

2011 ◽  
Vol 83 (3) ◽  
pp. 1045-1058 ◽  
Author(s):  
Paulo Michel P. Ferreira ◽  
Davi F. Farias ◽  
Martônio P. Viana ◽  
Terezinha M. Souza ◽  
Ilka M. Vasconcelos ◽  
...  
Keyword(s):  
Human Cancer ◽  
Ethanolic Extract ◽  
Cell Number ◽  
Northeastern Brazil ◽  
Human Cancer Cells ◽  
Ic50 Value ◽  
Underlying Mechanisms ◽  
Apoptotic Pathways ◽  
Seed Extracts

This study assessed the antiproliferative and cytotoxic potential against tumor lines of ethanolic seed extracts of 21 plant species belonging to different families from Northeastern Brazil. In addition, some underlying mechanisms involved in this cytotoxicity were also investigated. Among the 21 extracts tested, the MTT assay after 72 h of incubation demonstrated that only the ethanolic extract obtained from Myracrodruon urundeuva seeds (EEMUS), which has steroids, alkaloids and phenols, showed in vitro cytotoxic activity against human cancer cells, being 2-fold more active on leukemia HL-60 line [IC50 value of 12.5 (9.5-16.7) μg/mL] than on glioblastoma SF-295 [IC50 of 25.1 (17.3-36.3) μg/mL] and Sarcoma 180 cells [IC50 of 38.1 (33.5-43.4) μg/mL]. After 72h exposure, flow cytometric and morphological analyses of HL-60-treated cells showed that EEMUS caused decrease in cell number, volume and viability as well as internucleosomal DNA fragmentation in a dose-dependent way, suggesting that the EEMUS triggers apoptotic pathways of cell death.

Multicomponent 5-fluorouracil loaded PAMAM stabilized-silver nanocomposites synergistically induce apoptosis in human cancer cells

2015 ◽  
Vol 3 (3) ◽  
pp. 457-468 ◽  
Author(s):  
Ishita Matai ◽  
Abhay Sachdev ◽  
P. Gopinath
Keyword(s):  
Cancer Therapy ◽  
Cancer Cells ◽  
Therapeutic Agent ◽  
Human Cancer ◽  
Pamam Dendrimer ◽  
Human Cancer Cells ◽  
Silver Nanocomposites

Herein, we report the development of a poly(amidoamine) (PAMAM) dendrimer based multicomponent therapeutic agent forin vitrocancer therapy applications.

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